Copper metalloproteins comprise the primary oxidases, oxygenases and some of the oxygen carriers in animal cells. Our long range goal is the elucidation of the chemistry, metabolism, and biosynthesis of copper metalloproteins, with emphasis on ceruloplasmin, the blue copper protein of vertebrate serum which is a molecular link between iron and copper metabolism. Specific experimental approaches include: (1) a reexamination of the biological and enzymic activities of native, undegraded ceruloplasmin; (2) the molecular mechanisms of iron mobilization by ceruloplasmin; (3) the mechanism of bio-synthesis of ceruloplasmin and other copper proteins in liver and the effect of estrogens, transition metal ions, and other agents, both stimulatory and inhibitory, on the biosynthesis of copper proteins; (4) the copper transport function of ceruloplasmin and the use of its copper for the biosynthesis of cytochrome oxidase and other tissue copper proteins; (5) the evolutionary biochemistry of the copper proteins and the changes in copper metabolism during development and differentiation.